Hepatitis A / B / C / D / E

Hepatitis is an inflammation of the liver caused by exposure to toxins, immune diseases, or infection. Viruses cause most cases of hepatitis. Hepatitis A is inflammation of the liver caused by the hepatitis A virus. This is an acute (short-term) type of hepatitis, which usually requires no treatment.

According to the World Health Organization, 1.4 million cases of hepatitis A occur each year (WHO, 2012). This highly contagious form of hepatitis can cause epidemics through contaminated food or water. Luckily, it is not serious, and usually causes no long-term effects.

Hepatitis C is a disease that causes inflammation and infection in the liver. This condition develops after being infected with the Hepatitis C virus (HCV). There are two forms of hepatitis C: acute and chronic.

Acute hepatitis C causes symptoms to set in quickly, whereas chronic hepatitis C develops over a period of months, so symptoms may not be apparent at first. The World Health Organization (WHO) states that over 130 to 170 million people have chronic hepatitis C (WHO).

Unlike hepatitis A and B, hepatitis C has no vaccination, although efforts to create one are ongoing. Hepatitis C is highly contagious, which is why such a high number of people have the disease. According to WHO, this disease is found worldwide, with Egypt having the highest percentage of chronic hepatitis C cases (WHO).

Hepatitis D, also known as the delta virus, is an infection that causes your liver to swell. It is caused by the hepatitis D virus (HDV) and is uncommon in the United States.

Hepatitis D is one of many forms of hepatitis-other types include hepatitis A, B, C, and E. Unlike the other forms, hepatitis D cannot be contracted on its own. You can only contract hepatitis D if you are already infected with hepatitis B.

The symptoms of hepatitis B and hepatitis D are similar, so it can be difficult to tell which disease is causing your symptoms. Common symptoms include:

loss of appetite

fatigue

abdominal pains

yellowing of skin and eyes (jaundice)

joint pain

dark urine

vomiting

Hepatitis D can also cause the symptoms of hepatitis B to worsen, or appear in those who have been infected but haven`t yet developed symptoms.

The virus can be acute (short-term) or chronic (long-term). If you have chronic hepatitis D, you are at a higher risk of developing complications from the disease. Long-term or chronic hepatitis D might be present in your body for some time before the symptoms develop.

If you have the chronic form of hepatitis B, you are more likely to develop chronic hepatitis D.

Hepatitis E is a potentially serious acute disease. It is caused by the hepatitis E virus (HEV). The virus targets the liver.

According to the World Health Organization (WHO), 20 million cases of hepatitis E infection occur every year, and 57,000 of them result in death (WHO). It is more common in developing countries. Hepatitis E usually resolves itself but may develop into acute liver failure.

The symptoms of hepatitis E show up within several weeks of exposure. They includeyellowing of the skin (jaundice), dark urine, joint pain, and a loss of appetite. Pain in the abdomen, liver enlargement, and acute liver failure are also symptoms. Nausea, vomiting, fatigue, and fever can also occur.

NON ALCOHOLIC LIVER DISEASE

Nonalcoholic steatohepatitis or NASH is a common, often “silent” liver disease. It resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage. Most people with NASH feel well and are not aware that they have a liver problem. Nevertheless, NASH can be severe and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to work properly.

NASH affects 2 to 5 percent of Americans. An additional 10 to 20 percent of Americans have fat in their liver, but no inflammation or liver damage, a condition called “fatty liver.” Although having fat in the liver is not normal, by itself it probably causes little harm or permanent damage.

NASH is usually first suspected in a person who is found to have elevations in liver tests that are included in routine blood test panels, such as alanine aminotransferase (ALT) or aspartate aminotransferase (AST). When further evaluation shows no apparent reason for liver disease (such as medications, viral hepatitis, or excessive use of alcohol) and when x rays or imaging studies of the liver show fat, NASH is suspected. The only means of proving a diagnosis of NASH and separating it from simple fatty liver is a liver biopsy. For a liver biopsy, a needle is inserted through the skin to remove a small piece of the liver. NASH is diagnosed when examination of the tissue with a microscope shows fat along with inflammation and damage to liver cells. If the tissue shows fat without inflammation and damage, simple fatty liver or NAFLD is diagnosed. An important piece of information learned from the biopsy is whether scar tissue has developed in the liver. Currently, no blood tests or scans can reliably provide this information.

NASH is usually a silent disease with few or no symptoms. Patients generally feel well in the early stages and only begin to have symptoms—such as fatigue, weight loss, and weakness—once the disease is more advanced or cirrhosis develops. The progression of NASH can take years, even decades. The process can stop and, in some cases, reverse on its own without specific therapy. Or NASH can slowly worsen, causing scarring or “fibrosis” to appear and accumulate in the liver. As fibrosis worsens, cirrhosis develops; the liver becomes seriously scarred, hardened, and unable to function normally.

Not every person with NASH develops cirrhosis, but once serious scarring or cirrhosis is present, few treatments can halt the progression. A person with cirrhosis experiences fluid retention, muscle wasting, bleeding from the intestines, and liver failure. Liver transplantation is the only treatment for advanced cirrhosis with liver failure, and transplantation is increasingly performed in people with NASH. NASH ranks as one of the major causes of cirrhosis in America, behind hepatitis C and alcoholic liver disease.

Although NASH has become more common, its underlying cause is still not clear. It most often occurs in persons who are middle-aged and overweight or obese. Many patients with NASH have elevated blood lipids, such as cholesterol and triglycerides, and many have diabetes or pre-diabetes, but not every obese person or every patient with diabetes has NASH. Furthermore, some patients with NASH are not obese, do not have diabetes, and have normal blood cholesterol and lipids. NASH can occur without any apparent risk factor and can even occur in children. Thus, NASH is not simply obesity that affects the liver.

While the underlying reason for the liver injury that causes NASH is not known, several factors are possible candidates:

insulin resistance

release of toxic inflammatory proteins by fat cells (cytokines)

oxidative stress (deterioration of cells) inside liver cells

ALCOHOL RELATED LIVER ABNORMALITIES

The liver is one of the largest and most complex organs in the body. It stores vital energy and nutrients, manufactures proteins and enzymes necessary for good health, protects the body from disease, and breaks down (or metabolizes) and helps remove harmful toxins, like alcohol, from the body.

Because the liver is the chief organ responsible for metabolizing alcohol, it is especially vulnerable to alcohol-related injury. Even as few as three drinks at one time may have toxic effects on the liver when combined with certain over-the-counter medications, such as those containing acetaminophen.

This issue of Alcohol Alert examines the diagnosis and treatment of alcoholic liver disease (ALD), a serious and potentially fatal consequence of drinking alcohol. Another disorder, hepatitis C, also featured here, often is found in patients with ALD.

ALD includes three conditions: fatty liver, alcoholic hepatitis, and cirrhosis. Heavy drinking for as little as a few days can lead to “fatty” liver, or steatosis—the earliest stage of alcoholic liver disease and the most common alcohol-induced liver disorder. Steatosis is marked by an excessive buildup of fat inside liver cells. This condition can be reversed, however, when drinking stops.

Drinking heavily for longer periods may lead to a more severe, and potentially fatal condition, alcoholic hepatitis— an inflammation of the liver. Symptoms include nausea, lack of appetite, vomiting, fever, abdominal pain and tenderness, jaundice, and, sometimes, mental confusion. Scientists believe that if drinking continues, in some patients this inflammation eventually leads to alcoholic cirrhosis, in which healthy liver cells are replaced by scar tissue (fibrosis), leaving the liver unable to perform its vital functions.

Diagnosing ALD is a challenge. A history of heavy alcohol use along with certain physical signs and positive laboratory tests for liver disease are the best indicators of disease. Alcohol dependence is not necessarily a prerequisite for ALD, and ALD can be difficult to diagnose because patients often minimize or deny their alcohol abuse. Even more confounding is the fact that physical exams and lab findings may not specifically point to ALD (9).

Diagnosis typically relies on laboratory tests of three liver enzymes: gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Liver disease is the most likely diagnosis if the AST level is more than twice that of ALT (9), a ratio some studies have found in more than 80 percent of alcoholic liver disease patients. An elevated level of the liver enzyme GGT is another gauge of heavy alcohol use and liver injury. Of the three enzymes, GGT is the best indicator of excessive alcohol consumption, but GGT is present in many organs and is increased by other drugs as well, so high GGT levels do not necessarily mean the patient is abusing alcohol.

Lifestyle Changes. Abstinence from alcohol is vital to prevent further liver injury, scarring, and possibly liver cancer; it appears to benefit patients at each stage of the disease. Although only a few studies have looked specifically at the effects of abstinence on the progression of ALD, virtually every one has shown that abstaining from alcohol is beneficial (10,11).

Nutritional Treatment. Although alcoholic beverages contain calories, research suggests that under certain conditions these calories do not have as much value for the body as those derived from other nutrients (14). In addition, many alcoholics suffer from malnutrition, which can lead to liver damage and impaired liver function (15). Many drinkers take in less than the recommended daily amount of carbohydrates, proteins, fats, vitamins (A, C, and B, especially thiamine [B1]), and minerals (such as calcium and iron).

AUTOIMMUNE LIVER DISEASE

Autoimmune hepatitis is a disease in which the body’s immune system attacks liver cells. This immune response causes infl ammation of the liver, also called hepatitis. Researchers think a genetic factor may make some people more susceptible to autoimmune diseases. About 70 percent of those with autoimmune hepatitis are female.

The disease is usually quite serious and, if not treated, gets worse over time. Autoimmune hepatitis is typically chronic, meaning it can last for years, and can lead to cirrhosis—scarring and hardening—of the liver. Eventually, liver failure can result.

Autoimmune hepatitis is classified as type 1 or type 2. Type 1 is the most common form in North America. It can occur at any age but most often starts in adolescence or young adulthood. About half of those with type 1 have other autoimmune disorders, such as

type 1 diabetes

proliferative glomerulonephritis, an inflammation of blood vessels in the kidneys

thyroiditis, an inflammation of the thyroid gland

Graves’ disease, the leading cause of overactive thyroid

Sjögren’s syndrome, a syndrome that causes dry eyes and mouth

autoimmune anemia

ulcerative colitis, an inflammation of the colon and rectum leading to ulcers

Type 2 autoimmune hepatitis is less common, typically affecting girls aged 2 to 14, although adults can have it too.

One job of the immune system is to protect the body from viruses, bacteria, and other living organisms. The immune system usually does not react against the body’s own cells. However, sometimes it attacks the cells it is supposed to protect; this response is called autoimmunity. Researchers think certain bacteria, viruses, toxins, and drugs trigger an autoimmune response in people who are genetically susceptible to developing an autoimmune disorder.

Fatigue is probably the most common symptom of autoimmune hepatitis. Other symptoms include

an enlarged liver

jaundice

itching

skin rashes

joint pain

abdominal discomfort

spider angiomas, or abnormal blood vessels, on the skin

nausea

vomiting

loss of appetite

dark urine

pale or gray-colored stools

People in advanced stages of the disease are more likely to have symptoms related to chronic liver disease, such as fluid in the abdomen—also called ascites—and mental confusion. Women may stop having menstrual periods.

Symptoms of autoimmune hepatitis range from mild to severe. Because severe viral hepatitis or hepatitis caused by a drug—for example, certain antibiotics—have the same symptoms as autoimmune hepatitis, tests may be needed for an exact diagnosis. Doctors should also review and rule out all medicines a patient is taking before diagnosing autoimmune hepatitis.

The doctor will make a diagnosis based on symptoms, blood tests, and a liver biopsy.

Blood tests. A routine blood test for liver enzymes can help reveal a pattern typical of hepatitis, but further tests, especially for autoantibodies, are needed to diagnose autoimmune hepatitis. Antibodies are proteins made by the immune system to fight off bacteria and viruses. Autoantibodies attack the body’s cells. In autoimmune hepatitis, the immune system makes one or more types of autoantibodies. The most common are antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and antibodies to liver and kidney microsomes (anti-LKM). People with type 1 have ANA, SMA, or both, and people with type 2 have anti-LKM.

Liver biopsy. A tiny sample of liver tissue, examined with a microscope, can help doctors accurately diagnose autoimmune hepatitis and tell how serious it is. This procedure is done in a hospital or outpatient surgical facility.

CHOLESTATIC LIVER DISEASE

Primary biliary cirrhosis is a chronic disease that causes the bile ducts in the liver to become inflamed and damaged and, ultimately, disappear. Bile is a liquid produced in the liver that travels through the bile ducts to the gallbladder and then the small intestine, where it helps digest fats and fat-soluble vitamins A, D, E, and K. When the bile ducts become damaged from chronic inflammation, bile builds up in the liver, injuring liver tissue.

Normal liver and biliary system.

Injured liver tissue from chronic inflammation and the buildup of bile leads to cirrhosis, a condition in which the liver slowly deteriorates and malfunctions. Scar tissue replaces healthy liver tissue, partially blocking the flow of blood through the liver. Scarring also impairs the liver’s ability to

control infections

remove bacteria and toxins from the blood

process nutrients, hormones, and drugs

make proteins that regulate blood clotting

produce bile to help absorb fats— including cholesterol—and fat-soluble vitamins

The cause of primary biliary cirrhosis is unknown. Most research suggests the disease is an autoimmune condition. The immune system usually protects the body from harmful substances such as bacteria and viruses by attacking and destroying them. In autoimmune diseases, the immune system instead attacks the body’s own tissues. In primary biliary cirrhosis, the immune system attacks the bile ducts.

Genetic factors may make a person prone to develop primary biliary cirrhosis. Primary biliary cirrhosis is more common in people who have a parent or sibling—particularly an identical twin—with the disease.

Most people with primary biliary cirrhosis are diagnosed before symptoms begin. The first and most common symptoms people with this condition experience are

a general feeling of tiredness, or fatigue

pruritus—itchy skin—and darkened skin in itchy areas due to scratching

Other symptoms may develop, including

dry eyes and mouth

jaundice—darkening of the urine and yellowing of the skin and whites of the eyes—which occurs when the diseased liver does not remove enough bilirubin from the blood. Bilirubin is the pigment that gives bile its reddish-yellow color.

PSC is a disease that damages and blocks bile ducts inside and outside the liver. Bile is a liquid made in the liver. Bile ducts are tubes that carry bile out of the liver to the gallbladder and small intestine. In the intestine, bile helps break down fat in food.

In PSC, inflammation of the bile ducts leads to scar formation and narrowing of the ducts over time. As scarring increases, the ducts become blocked. As a result, bile builds up in the liver and damages liver cells. Eventually, scar tissue can spread throughout the liver, causing cirrhosis and liver failure.

PSC damages the hepatic, cystic, and common bile ducts, which carry bile out of the liver.

The main symptoms of PSC are itching, fatigue, and yellowing of the skin or whites of the eyes. An infection in the bile ducts can cause chills and fever. PSC progresses slowly, so a person can have the disease for years before symptoms develop.

Metabolic Liver Disease

Metabolic syndrome is considered to be a risk factor for cardiovascular diseases and type 2 diabetes that arises due to insulin resistance and an abnormal function and pattern of body fat. Insulin resistance refers to the diminished ability of cells to respond to the action of insulin in promoting the transport of the sugar glucose, from blood into muscles and other tissues.

Metabolic syndrome is a cluster of metabolic risk factors that come together in a single individual. These metabolic factors include insulin resistance, hypertension (high blood pressure), cholesterol abnormalities, and an increased risk for clotting. Patients are most often overweight or obese. An association between certain metabolic disorders and cardiovascular disease has been known since the 1940s.

Based on the guidelines from the National Heart, Lung, and Blood Institute (NHLBI) and the American Heart Association (AHA), any three of the following traits in the same individual meet the criteria for the metabolic syndrome:

HDL cholesterol 40mg/dl or lower in men and 50mg/dl or lower in women.

Abdominal obesity: a waist circumference of 102 cm (40 in) or more in men and 88 cm (35 inches) or more in women. For Asian Americans, the cutoff values are ≥90 cm (35 in) in men or ≥80 cm (32 in) in women

Some people may have symptoms of high blood sugar if diabetes - especially type 2 diabetes - is present. Symptoms of high blood sugar often include increased thirst; increased urination, especially at night; fatigue (tiredness); and blurred vision.

Metabolic syndrome is a group of risk factors that raises your risk for heart disease and other health problems, such as diabetesexternal link icon and stroke. These risk factors can increase your risk for health problems even if they're only moderately raised (borderline-high risk factors).

Most of the metabolic risk factors have no signs or symptoms, although a large waistline is a visible sign.

Genetic factors influence each individual component of the syndrome, and the syndrome itself. A family history that includes type 2 diabetes, hypertension, and early heart disease greatly increases the chance that an individual will develop the metabolic syndrome.

As is true with many medical conditions, genetics and the environment both play important roles in the development of the metabolic syndrome.

Environmental issues such as low activity level, sedentary lifestyle, and progressive weight gain also contribute significantly to the risk of developing the metabolic syndrome.

Padiatric Liver Disease

Wilson disease is a genetic disorder that prevents the body from getting rid of extra copper. A small amount of copper obtained from food is needed to stay healthy, but too much copper is poisonous. In Wilson disease, copper builds up in the liver, brain, eyes, and other organs. Over time, high copper levels can cause life-threatening organ damage.

People who get Wilson disease inherit two abnormal copies of the ATP7B gene, one from each parent. Wilson disease carriers, who have only one copy of the abnormal gene, do not have symptoms. Most people with Wilson disease have no known family history of the disease. A person’s chances of having Wilson disease increase if one or both parents have it.

About one in 40,000 people get Wilson disease.1 It equally affects men and women. Symptoms usually appear between ages 5 to 35, but new cases have been reported in people aged 2 to 72 years.

Wilson disease is caused by a buildup of copper in the body. Normally, copper from the diet is filtered out by the liver and released into bile, which flows out of the body through the gastrointestinal tract. People who have Wilson disease cannot release copper from the liver at a normal rate, due to a mutation of the ATP7B gene. When the copper storage capacity of the liver is exceeded, copper is released into the bloodstream and travels to other organs—including the brain, kidneys, and eyes.

Benign Liver Tumours

A tumor is an abnormal growth of cells or tissues. Some tumors are malignant, or cancerous. Others are benign, or noncancerous.

Cancerous liver tumors can be fatal. Most of the time, cancerous tumors in the liver started in another organ and spread to the liver. This form of liver cancer is called metastatic liver cancer. Cancerous liver tumors that start in the liver are relatively rare in the United States. This form of liver cancer is called primary liver cancer.

Noncancerous, or benign, liver tumors are common. They do not spread to other areas of the body, and they usually do not pose a serious health risk.

In most cases, benign liver tumors are not detected because they cause no symptoms. When they are detected, it is usually because a patient required a medical imaging test, such as an ultrasound, CT test or MRI, for another condition.

Hemangiomas are the most common form of benign liver tumors. They are a mass of abnormal blood vessels. Up to 5 percent of adults in the United States may have small hemangiomas in their liver. Women are more likely than men to develop them.

Usually these benign tumors produce no symptoms and do not need to be treated. In very rare cases, an infant with a large hemangioma may need to have it removed surgically to prevent clotting and heart failure.

Focal nodular hyperplasia is the second most common form of benign liver tumor after hemangiomas. These tumors occur mainly in women between the ages of 20 and 30. Like the other forms of benign liver tumors, they are generally discovered during imaging tests for other conditions.

Sometimes referred to as FNH, these tumors usually do not cause symptoms or require treatment. If they are large, doctors may recommend that they be removed surgically to avoid the risk of rupture, but this is very uncommon.

Hepatocellular adenomas are less common benign liver tumors. They occur most often in women of childbearing age. They used to be linked to oral contraceptives, when higher doses of estrogen were used.

Since these tumors generally do not cause symptoms, most are never detected. In rare cases, these tumors may rupture and bleed into the abdominal cavity. When doctors discover a large adenoma, they may recommend that it be surgically removed to prevent that possibility.

Hepatocellular adenomas may enlarge in women who take hormone pills, so doctors will often recommend discontinuing birth control pills or postmenopausal hormone replacement therapy to female patients who have this kind of tumor.

Liver Cancer Treatment

Cancer of the liver can be divided into primary liver cancer and secondary liver cancer:

Primary liver cancers (cancers that start in the liver)

-Hepatocellular carcinoma (HCC) / Hepatoma

This is the most common form of liver cancer in adults (about 9 in 10 cases). About 4 out of 5 cancers that start in the liver are this type. It is sometimes called hepatocellular carcinoma (HCC) as this type of cancer originates from a liver cell (hepatocyte) which becomes cancerous. (The bulk of the liver is made up from hepatocytes). A hepatoma most commonly develops as a complication of liver diseases such as cirrhosis (scarring of the liver) or types of hepatitis (liver inflammation).

-Bile duct cancer (cholangiocarcinoma)

Bile duct cancers account for 1 or 2 out of every 10 cases of liver cancer. These cancers can start in the small tubes (called bile ducts) that carry the bile that is made in the liver to the gallbladder or from the gallbladder to the intestines.

-Rare types of primary liver cancers

Angiosarcomas and hemangiosarcomas are rare cancers that start in the cells lining the blood vessels of the liver. These tumors grow quickly. Often by the time they are found they are too widespread to be removed. Treatment may help slow the disease, but these cancers are usually very hard to treat.

-Hepatoblastoma is a very rare kind of liver cancer that is usually found in children younger than 4 years old. About 2 out of 3 children with these tumors have good outcomes with surgery and chemotherapy, although the tumors are harder to treat if they have spread outside of the liver.

The place where a cancer starts is called the primary site. If a cancer starts somewhere else and then spreads to the liver, it is called secondary liver cancer. Secondary liver cancer is much more common than cancer that starts in the liver (primary liver cancer). Many common types of cancer, including colon, rectum, lung, and breast, spread to the liver. Secondary liver cancer is very different from primary liver cancer. The cancer cells still look and act like cancer cells from the part of the body that they came from, and they need treatments aimed at that kind of cancer, not liver cancer.

A cancerous tumour starts from one abnormal cell. The exact reason why a cell becomes cancerous is unclear. It is thought that something damages or alters certain genes in the cell. This makes the cell abnormal and multiply out of control. (See separate leaflet called What causes cancer? for more detail.)

Most people who develop a primary liver cancer have one or more of the following risk factors which seem to make liver cells more prone to becoming cancerous:

Cirrhosis. This is a condition which causes scarring of the liver. It tends to progress slowly. In the UK, the common causes of cirrhosis are heavy alcohol drinking, and infection with hepatitis C. However, there are various other causes of cirrhosis. Note: most people with cirrhosis do not develop liver cancer - it occurs in only a small number of people with cirrhosis.

Long-term infection with the hepatitis B or hepatitis C virus. It typically takes 20-30 years after first becoming infected to develop primary liver cancer. Infection with these viruses is not common in the UK, but it is becoming more common. However, these are common infections worldwide, particularly in Asia and Africa. Many young children in these areas are infected with the hepatitis B virus. This is why primary liver cancer is a common cancer in young adults in these areas of the world (developing 20-30 years after first being infected).

Ingesting some poisons or toxins. For example, a known risk factor is a poison called aflatoxin which contaminates some foods (for example, mouldy peanuts), mainly in developing countries.

Some conditions which cause persistent inflammation of the gut increase the risk slightly of developing a cholangiocarcinoma (an uncommon type of primary liver cancer) - for example, ulcerative colitis.

There is some evidence that smoking can increase the risk.

A parasitic infection (liver fluke) which mainly occurs in Africa and Asia increases the risk of developing a cholangiocarcinoma

There may be no symptoms in the early stage of the disease. As the cancer grows, the first symptoms to develop may be quite vague and nonspecific. For example, feeling generally unwell, feeling sick (nausea), loss of appetite, weight loss and tiredness. Many people who develop primary liver cancer will already have symptoms associated with cirrhosis. If you already have cirrhosis and your health becomes worse quite quickly, the cause may be a liver cancer which has developed.

As the cancer develops further, more specific symptoms which may also develop include:

Abdominal pain over the liver area.

Jaundice. Jaundice is when you go yellow. You tend to first notice it when the whites of the eyes become yellow. It is due to a build-up of the chemical bilirubin which is made in the liver. This occurs if the bile duct becomes blocked by the cancer. Bile and bilirubin cannot drain out from the liver and so leak into the bloodstream.

Itch (caused by the jaundice).

Swelling of the abdomen. This can be due to the growing cancer itself. It may also be due to ascites which is fluid that builds up in the abdomen which occurs with various liver disorders.

Screening using ultrasound, and sometimes also a blood test for alpha-fetoprotein (AFP), at 6- to 12-month intervals, has been recommended for people at high risk of liver cancer. This includes people with liver cirrhosis associated with infection with hepatitis B or hepatitis C virus. This can detect liver cancer at an earlier stage and therefore improve the chance of successful treatment.

Initial assessment

If liver cancer is suspected, you are likely to have a number of tests. These aim to:

Confirm that you have a cancer in the liver. Also, that the cancer is a primary liver cancer and not a secondary liver cancer.

Assess the stage of the cancer. That is, how much of the liver is affected and whether the cancer has spread to other parts of the body.

Assess the state of your liver function and your general health.

Therefore, a range of tests are usually needed. They may include:

Scans such as ultrasound scan, CT scan or MRI scan. These can help to show the exact location and extent of the cancer.

A liver biopsy. This is usually done to confirm the type of cancer. A biopsy is when a small sample of tissue is removed from a part of the body. The sample is then examined under the microscope to look for abnormal cells.

Blood tests help to assess the liver function and your general health.

Other tests may be done if the above do not clarify the situation. For example, alaparoscopy is sometimes done. This is a small operation to look inside the abdomen with a flexible telescope.

There are separate leaflets which describe each of these tests in more detail.

The main treatments used for primary liver cancer are surgery and chemotherapy. Other techniques are sometimes used. The treatment advised in each case depends on various factors such as:

The exact site of the primary tumour in the liver.

The stage of the cancer (how large the cancer is and whether it has spread). See also separate leaflet called Staging and grading cancer.

Your general health. In particular, the general state of your liver and liver function (many people with primary liver cancer also have poor liver function due to cirrhosis).

You should have a full discussion with a specialist who knows your case. They will be able to give you the pros and cons, likely success rate, the possible side-effects, and other details about the possible treatment options for your type of cancer.

You should also discuss with your specialist the aims of treatment. For example:

In some cases, treatment aims to cure the cancer. The best chance of a cure for primary liver cancer is when it is diagnosed and treated at an early stage. (Doctors tend to use the word remission rather than the word cured. Remission means there is no evidence of cancer following treatment. If you are in remission, you may be cured. However, in some cases a cancer returns months or years later. This is why doctors are sometimes reluctant to use the word cured.)

In some cases, treatment aims to control the cancer. If a cure is not realistic, with treatment it may be possible to limit the growth or spread of the cancer so that it progresses less rapidly. This may keep you free of symptoms for some time.

In some cases, treatment aims to ease symptoms (palliative treatment). For example, if a cancer is advanced then you may require painkillers or other treatments to help keep you free of pain or other symptoms. Some treatments may be used to reduce the size of a cancer, which may ease symptoms such as pain.

Surgery

Surgery which aims to cure the cancer is an option in some cases. If the cancer is small, has not spread outside the liver, and the rest of the liver is healthy, then it may be possible to cut out the part of the liver which contains the cancer. Healthy liver tissue will regrow to its full size within a few weeks if a section of liver is cut out. However, this operation is not suitable if your liver is damaged with severe cirrhosis (which is the case in many people with primary liver cancer).

A liver transplant is another option, but again only suitable for a small number of cases.

Surgery also has a role in palliative care. For example, if jaundice is severe, it may be possible to relieve the blockage of the bile by inserting a stent. This is a narrow tube which allows the bile to drain into the gut. Another example is to ease ascites (fluid in the abdomen) if it is severe. The ascites can be drained by inserting a tube through the wall of the abdomen.

Chemotherapy

Chemotherapy is a treatment which uses anti-cancer medicines to kill cancer cells, or to stop them from multiplying. It is not likely to be curative for primary liver cancer, but may shrink the tumour down to slow the progression of the disease.

There are new medicines being developed for the treatment of liver cancer. For example, sorafenib is a type of medicine called a multi-targeted kinase inhibitor. It interferes with the growth of cancer cells. Research has shown that sorafenib can be beneficial for people with advanced hepatocellular carcinoma. However, sorafenib is not currently recommended by the National Institute for Health and Clinical Excellence (NICE) for the treatment of people with advanced hepatocellular carcinoma.

Other treatments

Various other treatment techniques are sometimes used. For example:

Alcohol ablation. Ablation means to destroy. For this treatment, alcohol is injected into the tumour. The alcohol kills cancer cells.

Radiofrequency ablation. For this treatment, a needle is inserted into the tumour. High-intensity radio waves or laser light are then passed through the needle. This heats the cancer cells and kills them.

Cryotherapy. For this treatment, a small metal object filled with liquid nitrogen is placed into the tumour. The liquid nitrogen makes it very cold which destroys cancer cells.

Chemoembolisation. For this treatment, medicines used for chemotherapy are mixed with another oily chemical. The mixture is then injected into branches of the liver artery (hepatic artery) which are supplying the tumour with blood. The oily chemical helps to hold the chemotherapy medicines longer in the liver, and make them more effective in killing cancer cells.

Radiotherapy. This is a treatment which uses high-energy beams of radiation which are focused on cancerous tissue. This kills cancer cells, or stops cancer cells from multiplying. Radiotherapy is not often used for primary liver cancers apart form the uncommon cholangiocarcinoma type of cancer.

Liver Biopsy

A liver biopsy is a procedure that involves taking a small piece of liver tissue for examination with a microscope for signs of damage or disease. The three types of liver biopsy are the following:

Percutaneous biopsy the most common type of liver biopsy—involves inserting a hollow needle through the abdomen into the liver. The abdomen is the area between the chest and hips.

Transvenous biopsy involves making a small incision in the neck and inserting a needle through a hollow tube called a sheath through the jugular vein to the liver.

Laparoscopic biopsy involves inserting a laparoscope, a thin tube with a tiny video camera attached, through a small incision to look inside the body to view the surface of organs. The health care provider will insert a needle through a plastic, tubelike instrument called a cannula to remove the liver tissue sample.

People should talk with their health care provider about medical conditions they have and all prescribed and over-the-counter medications, vitamins, and supplements they take, including

antibiotics

antidepressants

aspirin

asthma medications

blood pressure medications

blood thinners

diabetes medications

dietary supplements

nonsteroidal anti-inflammatory drugs such as ibuprofen and naproxen

The health care provider may tell the person to stop taking medications temporarily that affect blood clotting or interact with anesthesia, which people sometimes receive during a liver biopsy.

Having blood tests. A person will have a test to show how well his or her blood clots. A person will have a test to show how well his or her blood clots. A technician or nurse draws a blood sample during an office visit or at a commercial facility and sends the sample to a lab for analysis. People with severe liver disease often have blood-clotting problems that can increase their chance of bleeding after the biopsy. A health care provider may give the person a medication called clotting factor concentrates just before a liver biopsy to reduce the chance of bleeding.

Arranging for a ride home after the procedure. For safety reasons, most people cannot drive home after the procedure. A health care provider will ask a person to make advance arrangements for getting home after the procedure.

Fasting before the procedure. A health care provider will ask a person not to eat or drink for 8 hours before the procedure if the provider anticipates using anesthesia or sedation.

A health care provider performs the liver biopsy at a hospital or an outpatient center and determines which type of biopsy is best for the person.

Percutaneous Liver Biopsy

A person lies face up on a table and rests the right hand above the head. A health care provider gives the person a local anesthetic on the area where he or she will insert the biopsy needle. If needed, the health care provider will give the person sedatives and pain medication.

The health care provider either taps on the abdomen to locate the liver or uses one of the following imaging techniques:

Percutaneous liver biopsy is the most common type of liver biopsy.

Ultrasound. Ultrasound uses a device, called a transducer, that bounces safe, painless sound waves off organs to create an image of their structure.

Computerized tomography (CT) scan. A CT scan uses a combination of x rays and computer technology to create images. For a CT scan, a technician may give the person a solution to drink and an injection of a special dye, called contrast medium. CT scans require the person to lie on a table that slides into a tunnel-shaped device where the technician takes the x rays.

Research has shown fewer complications after biopsy when health care providers use ultrasound to locate the liver compared with tapping on the abdomen.1 Health care providers may select ultrasound over a CT scan because it is quicker and less expensive, and can show the biopsy needle in real time.

The health care provider will

make a small incision in the right side of the person's abdomen, either toward the bottom of or just below the rib cage

insert the biopsy needle

ask the person to exhale and hold his or her breath while the health care provider inserts the needle and quickly removes a sample of liver tissue

insert and remove the needle several times if multiple samples are needed

place a bandage over the incision

After the biopsy, the person must lie on his or her right side for up to 2 hours to reduce the chance of bleeding. Medical staff monitors the person for signs of bleeding for 2 to 4 more hours.

Transvenous Liver Biopsy

When a person's blood clots slowly or the person has ascites—a buildup of fluid in the abdomen—the health care provider may perform a transvenous liver biopsy.

For this procedure, the person lies face up on an x-ray table, and a health care provider applies local anesthetic to one side of the neck. The health care provider will give sedatives and pain medication if the person needs them.

The health care provider will

make a small incision in the neck.

insert a sheath into the jugular vein and thread the sheath down the jugular vein, along the side of the heart, and into one of the veins in the liver.

inject contrast medium into the sheath and take an x ray. The contrast medium makes the blood vessels and the location of the sheath clearly visible on the x-ray images.

thread a biopsy needle through the sheath and into the liver and quickly remove a liver tissue sample.

insert and remove the biopsy needle several times if multiple samples are needed.

carefully withdraw the sheath and close the incision with a bandage.

Medical staff monitor the person for 4 to 6 hours afterwards for signs of bleeding.

Laparoscopic Liver Biopsy

Health care providers use this type of biopsy to obtain a tissue sample from a specific area or from multiple areas of the liver, or when the risk of spreading cancer or infection exists. A health care provider may take a liver tissue sample during laparoscopic surgery performed for other reasons, including liver surgery.

The person lies on his or her back on an operating table. A nurse or technician will insert an intravenous (IV) needle into the person's arm to give anesthesia. The health care provider will

make a small incision in the abdomen, just below the rib cage

insert a cannula into the incision and fill the abdomen with gas to provide space to work inside the abdominal cavity and to see the liver

insert a biopsy needle through the cannula and into the liver and quickly remove a liver tissue sample

insert and remove the biopsy needle several times if multiple samples are needed

remove the cannula and close the incisions with dissolvable stitches

The health care provider can easily spot any bleeding from the procedure with the camera on the laparoscope and treat it using an electric probe. The person stays at the hospital or an outpatient center for a few hours while the anesthesia wears off.

to avoid intense activity, exercise, or heavy lifting for up to 1 week.

soreness around the biopsy or incision site for about a week. Acetaminophen (Tylenol) or other pain medications that do not interfere with blood clotting may help. People should check with their health care provider before taking any pain medications.

a member of the health care team to review the discharge instructions with the person—or with an accompanying friend or family member if the person is still groggy—and provide a written copy. The person should follow all instructions given.

Liver biopsy results take a few days to come back. The liver sample goes to a pathology lab where a technician stains the tissue. Staining highlights important details within the liver tissue and helps identify any signs of liver disease. The pathologist—a doctor who specializes in diagnosing diseases—looks at the tissue with a microscope and sends a report to the person's health care provider.

Pain and bruising at the biopsy or incision site—the most common complication after a liver biopsy. Most people experience mild pain that does not require medication; however, some people need medications to relieve the pain.

Prolonged bleeding from the biopsy or incision site or internal bleeding. A person may require hospitalization, transfusions, and sometimes surgery or another procedure to stop the bleeding.

Infection of the biopsy site or incision site that may cause sepsis. Sepsis is an illness in which the body has a severe response to bacteria or a virus.

pneumothorax, also called collapsed lung, which occurs when air or gas builds up in the pleural space. The pleural space is thin layers of tissue that wrap around the outside of the lungs and line the inside of the chest cavity. Pneumothorax may happen when the biopsy needle punctures the pleural space.

hemothorax, or the buildup of blood in the pleural space.

puncture of other organs.

Ascitic Fluid Drainage

Ascites is the accumulation of fluid (usually serous fluid which is a pale yellow and clear fluid) in the abdominal (peritoneal) cavity. The abdominal cavity is located below the chest cavity, separated from it by the diaphragm. Ascitic fluid can have many sources such as liver disease, cancers, congestive heart failure, or kidney failure. Inside the abdomen there is a membrane called the peritoneum, which has two layers. One layer lines the abdominal wall and the other layer covers the organs inside the abdominal cavity. The peritoneum produces a fluid that acts as a lubricant and allows the abdominal organs to glide smoothly over one another. Sometimes too much of the fluid can build up between the two layers. Ascites is a symptom of many types of cancer and can also be caused by a number of conditions, such as advanced liver disease.

The most common cause of ascites is advanced liver disease or cirrhosis. Approximately 85% of the ascites cases are thought to be due to cirrhosis. Although the exact mechanism of ascites development is not completely understood, most theories suggest portal hypertension (increased pressure in the liver blood flow) as the main contributor.

Other factors that may contribute to ascites are salt and water retention. The circulating blood volume may be perceived low by the sensors in the kidneys as the formation of ascites may deplete some volume from the blood. This signals the kidneys to reabsorb more salt and water to compensate for the volume loss.

Some other causes of ascites related to increased pressure gradient are congestive heart failure and advanced kidney failure due to generalized retention of fluid in the body.

Acites can also manifest as a result of cancers, called malignant ascites. These types of ascites are typically manifestations of advanced cancers of the organs in the abdominal cavity, such as, colon cancer, pancreatic cancer, stomach cancer, breast cancer, lymphoma, lung cancer, or ovarian cancer.

Pancreatic ascites can be seen in people with chronic (long standing)pancreatitis or inflammation of the pancreas. The most common cause of chronic pancreatitis is prolonged alcohol abuse. Pancreatic ascites can also be caused by acute pancreatitis as well as trauma to the pancreas.

Traditionally, ascites is divided into 2 types; transudative or exudative. This classification is based on the amount of protein found in the fluid.

A more useful system has been developed based on the amount of albumin in the ascitic fluid compared to the serum albumin (albumin measured in the blood). This is called the Serum Ascites Albumin Gradient or SAAG.

The most common cause of ascites is cirrhosis of the liver. Many of the risk factors for developing ascites and cirrhosis are similar. The most common risk factors include hepatitis B, hepatitis C, and long standing alcohol abuse. Other potential risk factors are related to the other underlying conditions, such as congestive heart failure, malignancy, and kidney disease.

There may be no symptoms associated with ascites especially if it is mild (usually less than about 100 – 400 ml in adults). As more fluid accumulates, increased abdominal girth and size are commonly seen. Abdominal pain, discomfort, and bloating are also frequently seen as ascites becomes larger. Shortness of breath can also happen with large ascites due to increased pressure on the diaphragm and the migration of the fluid across the diaphragm causing pleural effusions (fluid around the lungs). A cosmetically disfiguring large belly, due to ascites, is also a common concern of some patients.

People with ascites should be routinely followed by their primary physician and any specialists that may be involved in their care. Gastroenterologists (specialists in gastrointestinal diseases) and hepatologist (liver specialists) commonly see patients with ascites due to liver disease. Other specialists can also care for patients with ascites based on the possible cause and the underlying condition. The specialists usually ask the patient to first contact their primary physician if ascites increase. If ascites is causing symptoms of shortness of breath, abdominal discomfort ,or inability to do normal daily tasks such as walking, the patient's primary doctor should be notified.

The diagnosis of ascites is based on physical examination in conjunction with a detailed medical history to ascertain the possible underlying causes since ascites is often considered a nonspecific symptom for other diseases. If ascites fluid is greater than 500ml, it can be demonstrated on physical examination by bulging flanks and fluid waves performed by the doctor examining the abdomen. Smaller amounts of fluid may be detected by an ultrasound of the abdomen. Occasionally, ascites is found incidentally by an ultrasound or aCT scan done for evaluating other conditions.

Diagnosis of underlying condition causing ascites is the most important part of understanding the reason for a person to develop ascites. The medical history may provide clues to the underlying cause and typically includes questions about previous diagnosis of liver disease, viral hepatitis infection and its risk factors, alcohol abuse, family history of liver disease, heart failure, cancer history, and medication history.

Blood work can play an essential role in evaluating the cause of ascites. A complete metabolic panel can detect patterns of liver injury, functional status of the liver and kidney, and electrolyte levels. A complete blood countis also useful by providing clues to underlying conditions. Coagulation (clotting) panel abnormalities (prothrombin time) may be abnormal because of liver dysfunction and inadequate production of clotting proteins.

Sometimes the possible underlying causes of ascites may not be determined based on the history, examination, and review of laboratory data and imaging studies. Analysis of the fluid may be necessary in order to obtain further diagnostic data. This procedure is called paracentesis, and it is performed by trained physicians. It involves sterilizing an area on the abdomen and, with the guidance of ultrasound, inserting a needle into the abdominal cavity and withdrawing fluid for further analysis.

For diagnostic purposes, a small amount (20cc, for example) may be enough for adequate testing. Larger amounts can be withdrawn if needed to reveal symptoms associated with increased abdominal ascites, up to a few liters (large volume paracentesis).

The analysis is done by sending the collected fluid to the laboratory promptly after drainage. Typically, the number and components of white blood cells and red blood cells (cell count), albumin level, gram stain and culture for any possible organisms, amylase level, glucose, total protein, and cytology (malignant or cancerous cells) are analyzed in the laboratory. The results are then analyzed by the treating doctor for further evaluation and determination of the possible cause of ascites.

The treatment of ascites largely depends on the underlying cause. For example, peritoneal carcinomatosis or malignant ascites may be treated by surgical resection of the cancer and chemotherapy, while management of ascites related to heart failure is directed toward treating heart failure with medical management and dietary restrictions.

Because cirrhosis of the liver is the main cause of ascites, it will be the main focus of this section.

Diet

Managing ascites in patients with cirrhosis typically involves limiting dietary sodium intake and the use of diuretics (water pills). Restricting dietary sodium (salt) intake to less than 2 grams per day is very practical, successful, and widely recommended for patients with ascites. In majority of cases, this approach needs to be combined with the use of diuretics as salt restriction alone is generally not an effective way to treat ascites. Consultation with a nutrition expert in regards to daily salt restriction can be very helpful for patients with ascites.

Medication

Diuretics increase water and salt excretion from the kidneys. The recommended diuretic regimen in the setting of liver related ascites is a combination of spironolactone (Aldactone) and furosemide (Lasix). Single daily dose of 100 milligrams of spironolactone and 40 milligrams of furosemide is the usual recommended initial dosage. This can be gradually increased to obtain appropriate response to the maximum dosage of 400 milligrams of spironolactone and 160 milligrams of furosemide, as long as the patient can tolerate the dose increase without any side effects. Taking these medications together in the morning is typically advised to preventfrequent urination during the night.

Therapeutic paracentesis

For patients who do not respond well to or cannot tolerate the above regimen, frequent therapeutic paracentesis (a needle carefully is placed into the abdominal area, under sterile conditions) can be performed to remove large amounts of fluids. A few liters (up to 4 to 5 liters) of fluid can be removed safely by this procedure each time. For patients with malignant ascites, this procedure may also be more effective than diuretic use.

Surgery

For more refractory cases, surgical procedures may be necessary to control the ascites. Transjugular intrahepatic portosystemic shunts (TIPS) is procedure done through the internal jugular vein (the main vein in the neck) under local anesthesia by an interventional radiologist. A shunt is placed between the portal venous system and the systemic venous system (veins returning blood back to the heart), thereby reducing the portal pressure. This procedure is reserved for patients who have minimal response to aggressive medical treatment. It has been shown to reduce ascites and either limit or eliminate the use of diuretics in a majority of cases performed. However, it is associated with significant complications such as hepaticencephalopathy (confusion) and even death.

More traditional shunt placements (peritoneovenous shunt and systemic portosystemic shunt) have been essentially abandoned due to their high rate of complications.

Liver transplant

Finally, liver transplantation for advanced cirrhosis may be considered a treatment for ascites due to liver failure. Liver transplant involves a verycomplicated and prolonged process and it requires very close monitoring and management by transplant specialists

Some complications of ascites can be related to its size. The accumulation of fluid may cause breathing difficulties by compressing the diaphragm and formation of pleural effusion.

Infections are another serious complication of ascites. In patients with ascites related to portal hypertension, bacteria from the gut may spontaneously invade the peritoneal fluid (ascites) and cause an infection. This is called spontaneous bacterial peritonitis or SBP. Antibodies are rare in ascites and, therefore, the immune response in the ascitic fluid is very limited. The diagnosis of SBP is made by performing a paracentesis and analyzing the fluid for the number of white blood cells or evidence of bacterial growth.

Hepatorenal syndrome is a rare, but serious and potentially deadly (average survival rates range from 2 weeks to about 3 months) complication of ascites related to cirrhosis of the liver leading to progressive kidney failure. The exact mechanism of this syndrome is not well known, but it may result from shifts in fluids, impaired blood flow to the kidneys, overuse of diuretics, and administration of contrasts or drugs that may be harmful to the kidney.

The prevention of ascites largely involves preventing the risk factors of the underlying conditions leading to ascites.

In patients with known advanced liver disease and cirrhosis of any cause, avoidance of alcohol intake can markedly reduce the risk of forming ascites.Nonsteroidal antiinflammatory drugs (ibuprofen [Advil, Motrin, etc.]) should also be limited in patients with cirrhosis as they may diminish the blood flow to the kidneys, thus, limiting the salt and water excretion. Complying with dietary salt restrictions is also another simple preventive measure to reduce ascites.

Endoscopic Management of Liver Diseases and Complications

The management of complications in liver disease is often complex and challenging. Endoscopy has undergone a period of rapid expansion with numerous novel and specialized endoscopic modalities that are of increasing value in the investigation and management of the patient with liver disease. It is clear that the role of the endoscopy in liver disease is well beyond that of just treating varices. As the technology in endoscopy expands, so does the role of the endoscopist in liver disease.

Liver disease and cirrhosis are common causes of mortality worldwide[1]. The role of endoscopy in liver disease is both diagnostic and interventional: endoscopy should be offered to patients with relevant symptoms (unsuspected liver disease may be diagnosed in this manner) and for variceal screening and treatment. Patients with liver disease can be challenging to sedate, and the complexity of endoscopy in liver disease continues to increase with rising numbers of patients with a liver transplant, and the advent of new endoscopic modalities such as capsule endoscopy and endoscopic ultrasound (EUS).

This will depend on why you did not get placed on the waiting list. For some patients it is too soon to consider the transplant option; for others there may be concerns as to their ability to survive a liver transplant.

Part of the assessment involves your family (or carer) coming to Birmingham to meet the transplant co-ordinators so that a plan for your care after hospital can be agreed. You will not be added to the waiting list until this has happened.